Recent developments in quantitative SERS: moving towards absolute quantification

Surface-enhanced Raman scattering (SERS) generates molecularly specific fingerprints of analytes and when the experimental conditions are carefully controlled this is highly quantitative. This review critiques the development of quantitative SERS from simple univariate assessment of single vibrational modes to multivariate analysis of the whole spectrum for improved quantification. SERS has also been developed for direct multiplex detection and quantification of multiple analytes and this is also discussed, as is the need for LC-SERS for analyte separation should multivariate chemometric approaches fail to effect quantification. Finally, to effect absolute quantification with SERS, the concepts of isotopologues is introduced along with the standard addition method (SAM) and suitable examples that have been developed and exploit these techniques are presented. We believe that SERS will be routinely used for quantitative analysis and it is only a matter of time before this technique translates from the laboratory to the clinical environment.